Safety and Efficacy of Eltrombopag at Escalated Doses

NCT01880047 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 116862
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Study rationale is based on the data that in previous clinical studies of eltrombopag in ITP there are some patients who have been reported as non responders at the maximal approved dose of 75 mg daily. The trend in both normal volunteers and in patients with ITP suggest and increasing response rate with increased doses of eltrombopag up to a dose of 75mg. Previously published data has shown no overt increase in toxicity in normal volunteers, oncology patients and aplastic anemia patients treated with escalated doses as high or higher than those proposed in this study. It therefore seems possible that in ITP patients who did not respond to a dose of 75mg daily, eltrombopag could be more effective at a higher dose. We propose a double blind randomized controlled trial in ITP patients who have been defined as non-responders at the maximum dose (75mg) of eltrombopag, assessing efficacy and toxicity at higher daily doses (100mg, 125 mg, 150 mg)

Conditions

Immune Thrombocytopenia; Platelet Disorder

Keywords

Immune Thrombocytopenia; ITP; Eltrombopag; Promacta

Outcome Measures

Primary Outcomes (1)

• Number of Patients Responding to >75mg Daily as Defined by a Rise in Platelet Count by 20,000/Microliter, With a Total Platelet Count >50,000/Microliter, ON TWO CONSECUTIVE OCCASIONS During the 8 Week Period

  To determine if patients with chronic ITP who do not respond to 75 mg of eltrombopag daily given for at least 3 weeks but then do respond to eltrombopag given daily first for 2 weeks at doses of 100, then for 2 weeks at 125 mg and finally for 4 weeks at a dose of 150mg daily. Response will be defined as 2 consecutive platelet counts of \> 50,000 with an increase of \> 20,000 from the study baseline within the 8 week increased dose window not as a result of rescue treatment.

  8 weeks

Secondary Outcomes (1)

• Number of Particiapants With Drug Related Adverse Events

  8 weeks

Study Arms (2)

Eltrombopag

ACTIVE COMPARATOR

Subjects in the study will receive 75 mg eltrombopag and then be randomized to receive either an additional 25 mg of eltrombopag or matching placebo tablet dispensed by the research pharmacy. Subjects and investigators will be blinded to randomization. Randomization will be stratified according to splenectomy status. Randomization will be performed at the time of informed consent with a computer generated randomization table. Subjects and investigators will be blinded to assignment and treatment in this phase.

Drug: Eltrombopag

Placebo

PLACEBO COMPARATOR

Subjects will be randomly allocated in a two to one ratio to receive treatment or placebo. All subjects in the study will receive 75 mg eltrombopag and then be randomized to receive either an additional 25 mg of eltrombopag or matching placebo tablet dispensed by the research pharmacy. Subjects and investigators will be blinded to randomization. Randomization will be stratified according to splenectomy status.

Drug: Placebo

Interventions

Eltrombopag DRUG

Eltrombopag will be administered for 8 weeks or until the platelet count exceeds 150,000; at this point dosing will stop, subject will be considered a responder and the subject will eligible for entering Part 2 (the long term treatment part of the study. The dose at which the subject achieved the primary endpoint (\> 50,000 and increase by \> 20,000) will be considered the dose of response. Dose escalation will continue, despite satisfaction of the primary endpoint of study (\> 50,000 and \> 20,000 above baseline), unless the platelet count reaches the lower limit of normal range 150,000. Subjects will stop study medication if the platelet count is within the normal range, thereby minimizing any safety risk associated with elevated platelet count.

Also known as: SB-497115-GR, Promacta

Eltrombopag

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject or their parent/ guardian has signed and dated a written informed consent
• Male and Females aged 12 years or older diagnosed with chronic ITP according to the new consensus guidelines
• No indication of a disease which may cause thrombocytopenia other than ITP----no specific testing required
• Subjects with thrombocytopenia ≤ 50,000 /uL after at least 21 days of daily dosage with eltrombopag 75mg
• Stable dosage of concomitant treatments for ITP
• ≥ 2 weeks or longer (corticosteroids);
• At least 2 weeks from rescue therapy for ITP (WinRho, Intravenous Immunoglobulin (IVIG), corticosteroids, platelet transfusion)
• At least 4 weeks from rituximab treatment
• Pregnant or Lactating Women are excluded
• Women of child-bearing age with a negative pregnancy test within 7 days of enrollment and who agree to use acceptable methods of birth control will be eligible for this study
• Female subjects or female partners of male subjects must either be of non-child bearing potential (hysterectomy, bilateral ovariectomy, bilateral tubal ligation or post menopausal for more than one year) OR, if of child bearing potential, using one of the following highly effective methods of contraception.
• complete abstinence from intercourse
• Intrauterine device (IUD)
• Two forms of barrier contraception. diaphragm plus spermicide, or for males condoms plus spermicide.
• Male partner is sterile and is the only partner of the female.

You may not qualify if:

• Previous history of eltrombopag-related liver function test (LFT) elevation that required interruption of treatment
• Previous history of immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag
• HIV Infection
• History of Arterial of Venous Thrombosis within the past year or requiring ongoing therapy
• Active Hepatitis C infection
• Treatment with medications that affect platelet function ( including but not limited to Aspirin, Clopidogrel and /or NSAIDs) or anti-coagulant medications
• Elevated Aspartate Aminotransferase(AST/ALT) or Creatinine \> 1.5 times upper limit of normal in 4 weeks prior to enrollment\*
• Abnormalities in white blood cell count (WBC), automatic neutrophil count (ANC), and Hemoglobin \> 1.5 times upper or lower limit of normal\*
• \* Subjects can be rescreened to be included

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Novartis: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Sujit Sheth
• Organization: Weill Cornell Medicine

shethsu@med.cornell.edu

2126463400

Study Officials

• Sujit Sheth, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: June 18, 2013
• Study Start: February 1, 2013
• Primary Completion: February 15, 2017
• Study Completion: October 16, 2017
• Last Updated: June 11, 2019
• Results First Posted: June 11, 2019

Record last verified: 2019-05

Locations

US (1)